HMG-CoA reductase inhibitors, popularly known as statins, are among the most widely prescribed lipid—lowering drugs.
Chemically rosuvastatin is (+)-(3R,5S)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino) pyrimidin-5-yl]3,5-dihydroxy-6(E)-heptenoic acid calcium salt (2:1) having the structural formula I.

Rosuvastatin is an antihypercholesterolemic drug used in the treatment of atherosclerosis.
Hypercholesterolemia is now well recognized as a primary risk in coronary heart disease. Clinical studies with lipid lowering agents have established that decreasing elevated serum cholesterol level reduces the incidence of cardiovascular mortality. Recently, it has been found that rosuvastatin calcium has consistently shown greater potency than other currently marketed statins (atorvastatin, simvastatin and pravastatin) in preclinical and clinical testing.
Rosuvastatin and a process for its preparation is disclosed in U.S. Pat. No. 5,260,440. The process disclosed therein involves four distinct chemical steps: (1) condensation of methyl (3R)-3-[(tert-butyldimethylsilyl) oxy]-5-oxo-6-triphenylphosphoranyli-dene hexanoate with 4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino)-5-pyrimidinecarboxaldehyde; (2) deprotection of the 3-hydroxyl group to give the keto alcohol; (3) reduction of 5-oxo to get the chiral dihydroxy heptenoate; and (4) hydrolysis of the dihydroxy heptenoate.
The generation of the phosphorane side chain requires eight synthetic steps and involves expensive reagents. The process is both uneconomical and time consuming, hence not suitable for commercial production.
It is, therefore, desirable to provide an efficient process for the preparation of rosuvastatin which improves the economics by employing less expensive reagents and is more productive.